Evaluation of Pharmacokinetics, Immunogenicity, and Immunotoxicity of DNA Tetrahedral and DNA Polymeric Nanostructures

Author:

Guo Yanfei12,Huang Yan1,Liu Mingxing1,Liu Jinjian3,Liu Jianfeng3,Yang Dayong12ORCID

Affiliation:

1. Frontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) School of Chemical Engineering and Technology Tianjin University Tianjin 300350 P. R. China

2. Department of Chemistry State Key Laboratory of Molecular Engineering of Polymers Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials College of Chemistry and Materials Fudan University Shanghai 200438 P. R. China

3. State Key Laboratory of Advanced Medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Key Laboratory of Radiopharmacokinetics for Innovative Drugs Tianjin Institutes of Health Science Institute of Radiation Medicine Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin 300192 P. R. China

Abstract

AbstractDeoxyribonucleic acid (DNA) nanostructures have been extensively explored in biomedical applications and have emerged as a promising platform for drug delivery, bioanalysis, and therapeutics. Their in vivo behaviors have received much attention, a prerequisite for clinical applications. Herein, the pharmacokinetics, immunogenicity, and immunotoxicity of two representative DNA nanostructures: DNA tetrahedron (TDN) and DNA nanoparticle (DNP) are studied. The pharmacokinetics of DNA nanostructures are monitored in a mouse model via tracking of 32P radiolabeled, and the half‐lives of TDN and DNP are 9.88 and 19.80 min, respectively. TDN and DNP preferentially accumulate in the liver and kidney in one half‐life and are metabolized through liver, kidney, and excreta after 24 h. Meanwhile, TDN and DNP elicit a weak pro‐inflammatory immune response with low immunogenicity and are non‐immunotoxic, as shown by immunotoxicity evaluation, histopathology, and serum biochemical index analysis. This research shows that the DNA nanostructures of TDN and DNP are safe for biological systems, indicating that TDN and DNP can be developed as promising therapeutic platforms in biomedicine.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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